To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
 Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
 Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
 Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
Animals ; Disease Models, Animal ; Doxorubicin ; Glomerulosclerosis, Focal Segmental ; chemically induced ; Kidney ; drug effects ; Mice ; Mice, Inbred NOD ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Xanthones ; pharmacology ; therapeutic use

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bibenzyls ; chemistry ; pharmacology ; therapeutic use ; Diphosphates ; chemistry ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; Oligopeptides ; chemistry ; pharmacology ; therapeutic use ; Organophosphorus Compounds ; chemistry ; pharmacology ; therapeutic use ; Serine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Stilbenes ; chemistry ; pharmacology ; therapeutic use ; Tubulin Modulators ; chemistry ; pharmacology ; therapeutic use ; Xanthones ; chemistry ; pharmacology ; therapeutic use

To explore gambogenic acid (GNA)-induced apoptosis and underlying mechanism in vivo. A549 nude mice xenografts were used as in vivo model to study anticancer effect of GNA by observing tumor growth curve and weight of the tumor. Ultrastructure of A549 cells treated by GNA was observed by TE. Expression of COX-2 and VEGF were detected by immunohistochemistry. TUNEL assay was applied in examining apoptosis index of tumor cells. The tumor isolated from mice treated by GNA (8, 16 mg kg(-1)) took on a slow growth condition compared with control group. The results suggested that weight and volume of the tumor from experimental groups were remarkably decreased compared with control group (P < 0.05). Ultrastructure change of the tumor, such as vacuolization, abnormal distribution of the heterochromosome, volume of the tumor cells, even apoptotic bodies, were observed in GNA-treated group. While no apparent morphological change was observed in the normal group. Typical apoptotic characteristics could be distinctly observed in the mouse treated by GNA for 20 days and apoptosis index in GNA-treated group was significantly higher than model group. Expression of COX-2 and VEGF were significantly down-regulated in GNA-treated groups in comparison with control group (P < 0.01). These results indicate that GNA could affect the development and progression of A549 cells through inducing apoptosis, mediating the expression of VEGF in vascular cells and COX-2 in tumor cells.
Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Lung Neoplasms ; drug therapy ; metabolism ; ultrastructure ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron, Transmission ; Terpenes ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism ; Xanthenes ; Xanthones ; therapeutic use ; Xenograft Model Antitumor Assays

OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects* ; Apoptosis Regulatory Proteins/immunology* ; Autophagy/immunology* ; bcl-2-Associated X Protein/immunology* ; Bortezomib/therapeutic use* ; Burkitt Lymphoma/immunology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Drug Therapy, Combination ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 ; Receptors, CXCR/immunology* ; RNA, Messenger ; TOR Serine-Threonine Kinases ; Xanthones/therapeutic use*

Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.
Androstenedione ; analogs & derivatives ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Aromatase ; chemistry ; metabolism ; pharmacology ; Aromatase Inhibitors ; chemistry ; classification ; pharmacology ; therapeutic use ; Breast Neoplasms ; drug therapy ; Catalysis ; Coumarins ; chemistry ; pharmacology ; Estrogens ; biosynthesis ; Flavonoids ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Nitriles ; chemistry ; pharmacology ; Sesquiterpenes ; chemistry ; pharmacology ; Structure-Activity Relationship ; Triazoles ; chemistry ; pharmacology ; Xanthones ; chemistry ; pharmacology

In order to investigate the antiviral effect of chinonin against Herpes simplex virus (HSV), the encephalitis model in mice and skin infection model in guinea pigs were established by HSV- I and HSV-II infection respectively. Acyclovir was used as the positive reference drug to evaluate the antiviral capacity of chinonin. Chinonin showed an obvious therapeutic effect on encephalitis in mice at doses of 25 and 50 mg/kg. At both dosages, chinonin demonstrated stronger protection than acyclovir (1 and 5 mg/kg) to the infected mice from death. It was also found that chinonin could treat the skin infection in guinea pigs effectively. The therapeutic effect of chinonin was similar to that of acyclovir (5 mg/kg) at 25 mg/kg but obviously better than that at 50 and 75 mg/ kg. In conclusion, chinonin is a potential candidate for the treatment against HSV.
Acyclovir ; therapeutic use ; Animals ; Antiviral Agents ; pharmacology ; Encephalitis ; drug therapy ; virology ; Glycosides ; pharmacology ; Guinea Pigs ; Herpes Simplex ; drug therapy ; Herpesvirus 1, Human ; drug effects ; Herpesvirus 2, Human ; drug effects ; Mice ; Simplexvirus ; drug effects ; Skin Diseases, Infectious ; drug therapy ; Xanthenes ; pharmacology ; Xanthones

OBJECTIVETo investigate mechanism of inhibition on the lipopolysaccharide induced chronic inflammation of mangiferin by the regulation of mitogen-activated protein kinase (MAPK) signaling pathway.

METHODSixty SD rats were randomly divided into normal control, model control, positive drug control (prednisone, 5 mg x kg(-10 x d(-1)) and mangiferin (200, 100, 50 mg x kg(-1) x d(-1)) group. The chronic inflammation models were established by intermittent injection of lipopolysaccharide via the tail vein. The leucocyte count was measured. The levels of serum tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) were detected by enzyme-linked immunosorbent assay (ELISA). The reverse transcription-polymerase chain reaction (RT-PCR) was applied to evaluate the expressions of p38, ERK, JNK gene of leucocyte in MAPK signaling pathway.

RESULTCompared with the model control, not only the leucocyte count and the level of serum TNF-alpha, IL-6, sICAM-1 but also the expressions of ERK, JNK gene of leukocyte were markedly reduced in mangiferin (200 mg x kg(-1) x d(-1)) group (P < 0.05). However, there was no statistics significance for the expression of p38 gene between the model control and the mangiferin (200 mg x kg(-1) x d(-1)) group.

CONCLUSIONAs a possible mechanism, the regulation of mangiferin on the expressions of ERK, JNK gene of leukocyte in MAPK signaling pathway was involved in its great inhibition on the chronic inflammation induced by lipopolysaccharide.

Animals ; Chronic Disease ; Gene Expression ; Inflammation ; chemically induced ; drug therapy ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-6 ; blood ; Leukocyte Count ; Leukocytes ; metabolism ; Lipopolysaccharides ; toxicity ; MAP Kinase Signaling System ; drug effects ; genetics ; Male ; Mangifera ; chemistry ; Mitogen-Activated Protein Kinases ; genetics ; Models, Animal ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood ; Xanthones ; pharmacology ; therapeutic use